Bayer to Evaluate Riociguat in Children Suffering from Pulmonary Arterial Hypertension (PAH)

News Release

Berlin, October 7, 2015 – Bayer announced today the initiation of a phase III trial to evaluate the safety and tolerability of riociguat in children suffering from pulmonary arterial hypertension (PAH). Riociguat has been approved since 2013 for the treatment of adults suffering from this life-threatening disorder of the lungs. The development and commercialization of riociguat is part of the worldwide strategic collaboration with MSD (through a subsidiary) in the field of soluble guanylate cyclase (sGC) modulation. MSD is known as Merck in the U.S. and Canada.

“Taking into account the poor prognosis for children with pulmonary arterial hypertension, new medications are needed,” said Dr. Joerg Moeller, Member of the Bayer HealthCare Executive Committee and Head of Global Development. “In clinical studies riociguat has proven to be effective and well tolerated for adults, and now with our new study we will investigate its safety profile in children suffering from pulmonary hypertension.”

Pulmonary hypertension (PH) can occur at any age from infancy to adulthood. Data on pediatric epidemiology remain rare and the exact incidence and prevalence of PH in children is not known. Until now, there are only two approved treatment options for children with PAH.

PATENT-CHILD is an international, multicenter, single-arm, open-label study to evaluate the safety, tolerability and pharmacokinetics of a body-weight adjusted riociguat regimen in children aged between 6 years and less than 18 years of age who have been diagnosed with idiopathic PAH, hereditary PAH, or PAH associated with connective tissue disease or congenital heart disease with shunt closure.

About Pulmonary Arterial HypertensionPulmonary arterial hypertension (PAH), one of the five types of PH, is a progressive and life-threatening disease in which the blood pressure in the pulmonary arteries is significantly increased due to vasoconstriction and which can lead to right heart failure and death. PAH is characterized by morphological changes to the endothelium of the arteries of the lungs causing remodeling of the tissue and vasoconstriction. As a result of these changes, the blood vessels in the lungs constrict, making it more difficult for the heart to pump blood through to the lungs. PAH is a rare disease and affects an estimated 15-52 people per million globally. It is more prevalent in women than men. In most cases, PAH has no known cause, though it can sometimes be inherited.

In spite of several pharmacological treatment options for PAH having been available for over a decade, the prognosis for these patients has remained poor, resulting in the need for effective alternative treatment options. Currently, mortality of PAH patients remains high and is still 15% at 1 year and 32% at 3 years after diagnosis.

About RiociguatRiociguat is a soluble guanylate cyclase (sGC) stimulator, the first member of a distinct class of compounds discovered and developed by Bayer as an oral treatment to target a key molecular mechanism underlying PH. Riociguat is being investigated as a specific approach to treat different types of PH. sGC is an enzyme found in the endothelial cells and the receptor for nitric oxide (NO). When NO binds to sGC, the enzyme enhances synthesis of the signaling molecule cyclic guanosine monophosphate (cGMP). cGMP plays an important role in regulating vascular tone, proliferation, fibrosis, and inflammation.

PH is associated with endothelial dysfunction, impaired synthesis of NO and insufficient stimulation of sGC. Riociguat has a dual mode of action – it sensitizes sGC to endogenous NO by stabilizing the NO-sGC binding. Riociguat also directly stimulates sGC via a different binding site, independently of NO. Riociguat, as a stimulator of sGC, addresses the issue of NO deficiency by restoring the NO-sGC-cGMP pathway, leading to increased generation of cGMP.

With its distinct mode of action, riociguat has the potential to overcome a number of limitations of other approved therapies for PAH, including NO dependence, and is the first drug which has shown clinical benefits in patients with inoperable CTEPH or persistent or recurrent CTEPH after surgery, where until the approval of riociguat no approved pharmacologic treatment was available.

Riociguat was approved under the name Adempas® in the US for use in inoperable CTEPH or persistent or recurrent CTEPH after surgery and in PAH in October 2013. In the EU and US, riociguat has been granted orphan drug designation and was approved by the European Medicines Agency (EMA) under the name Adempas® for use in CTEPH and PAH in March 2014. In Japan, riociguat has been granted orphan drug designation in the CTEPH indication and was approved in CTEPH in January 2014 and in PAH in February 2015.

Since October 2014, the worldwide strategic collaboration with MSD (known as Merck in the U.S. and in Canada) in the field of sGC modulators brings together the two leading companies in this field, who both have the stated intent to make full use of this promising novel class of compounds and the potential it holds for the benefit of patients. Riociguat, the first sGC stimulator approved and made available to patients, is the first product which is part of this collaboration.

About Bayer HealthCareThe Bayer Group is a global enterprise with core competencies in the fields of health care and agriculture. Bayer HealthCare, a subgroup of Bayer AG with annual sales of around EUR 20.0 billion (2014), is one of the world’s leading, innovative companies in the healthcare and medical products industry and is based in Leverkusen, Germany. The company combines the global activities of the Animal Health, Consumer Care, Medical Care and Pharmaceuticals divisions. Bayer HealthCare’s aim is to discover, develop, manufacture and market products that will improve human and animal health worldwide. Bayer HealthCare has a global workforce of 60,700 employees (Dec 31, 2014) and is represented in more than 100 countries. More information is available www.healthcare.bayer.com.

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